ArticleScientific reports2025
Single-cell RNA sequencing and Mendelian randomization, revealing molecular mechanisms and causal correlation of immune-related genes in periodontitis.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The immune system has been linked to periodontitis risk in oral inflammation and systemic consequences. Specifically, this study investigated whether hub genes were associated with immune cells via integrating single-cell RNA sequencing (scRNA-seq) and Mendelian randomization (MR). We analyzed scRNA-seq data to identify differentially expressed genes (DEGs) and immune cell subtypes in periodontitis. First, MR analysis was conducted using eQTL data to determine causal relationships between immune cell gene expression and periodontitis risk. Then, Gene ontology (GO) and pathway enrichment analyses were performed to understand functional implications. In addition, CellChat trajectory analysis explored intercellular communication. Finally, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) were used to validate hub genes. Comprehensive bioinformatics analysis delineated 23 immunologically distinct cell populations and identified 7 pivotal regulatory genes (ANXA1, ARL4C, CD79B, LRRC25, NKG7, SLC11A1, and VIM) demonstrating significant causal associations with periodontitis pathogenesis. Functional pathway analysis demonstrated these molecular markers participate in critical immunomodulatory pathways. RT-qPCR validation confirmed concordance between mRNA expression patterns of these DEGs and MR findings. Immunohistochemical analysis substantiated the causal relationships predicted by MR analysis, showing positive correlations for ANXA1 and SLC11A1 expression, while CD79B exhibited an inverse association. Advanced computational modeling of immune cell receptor-ligand interactions and cellular communication networks uncovered distinct functional roles during periodontitis development, providing novel insights into disease progression mechanisms. This study highlights the crucial role of immune cells and hub genes in periodontitis. These findings provide valuable insights into immune-related mechanisms and potential interventions for periodontitis.
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